Progesterone, like other steroid hormones, is bound with high affinity by specific protein receptors in the cytoplasm of cells in the uterus. The complex of progesterone and its receptor then moves into the nucleus and binds to nuclear chromatin, thus initiating the biochemical actions characteistic of the hormone. The movement of the progesterone-receptor complex from cytoplasm to nucleus decreases the concentration of cytoplasmic receptors. Steroid hormone receptors in the cytoplasm are eventually replenished, either by the release and reuse of receptors from the nucleus, or the biosynthesis of new receptors, or both. However, the movement of progesterone receptors between cytoplasm and nucleus has not been studied in detail. Progesterone acts on the uterus in synergism with estrogen, probably because the progesterone receptor is induced by estrogen. During the course of action, progesterone undergoes reductive metabolism in the uterus. The first, and rate limiting step, the conversion of progesterone to 5alpha-pregnane-3,20-dione, takes place in the nucleus and is stimulated by estrogen. Further reduction takes place in the cytoplasm. We are studying: 1) the movement of the progesterone receptor between uterine cytoplasm and nucleus after the administration of progesterone, and 2) the metabolism of progesterone in the uterus and the distribution of metabolites between cytoplasm and nucleus. BIBLIOGRAPHIC REFERENCES: Binding of Progesterone Receptor by Nuclear Preparations of Rabbit and Guinea Pig Uterus, Saffran, J., Loeser, B.K., Bohnett, S.A., and Faber, L.E. J. Biol. Chem 251: 5607, 1976. Mammalian Progesterone Receptors: Biosynthesis Structure and Nuclear Binding, Faber, L.E., Saffran, J., Chen, T.H. and Leavitt, W.W., Current Topics in Molecular Endocrinology 4: 68, 1976.